title: Discovery of a new class of immunosuppressants from Trichothecium roseum co-inspired by cross-kingdom similarity in innate immunity and pharmacophore motif.
abstract: The limited selection of immunosuppressants in the clinic hampers the efficient management of immune disorders such as rejections after organ transplantations. However, the search for new immunosuppressive compounds remains random and creates inevitably financial and laborious wastes. Herein, we present an immunity-inspired discovery strategy that rationally allows an efficient identification of immunosuppressive compounds from the endophyte culture, as exemplified by the new peptide trichomide A. This compound exerts its immunosuppressive action more selectively than cyclosporin A. It was found that trichomide A decreases the expression of Bcl-2, increases the expression of Bax, and has a small or negligible effect on the expressions of p-Akt, CD25, and CD69. Our study strengthens the idea that the cross-kingdom similarity in immunity among living things could provide a shorter route towards the identification of natural products valuable for the development of new immunosuppressants.
authors.affiliation: Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, 22 Hankou Road, Nanjing, 210093 (P. R. China), Fax: (+86) 25-8330 2728.
authors.forename: Ai Hua
authors.initials: AH
authors.lastname: Zhang
authors.forename: Xing Qi
authors.initials: XQ
authors.lastname: Wang
authors.forename: Wen Bo
authors.initials: WB
authors.lastname: Han
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.forename: Ye
authors.initials: Y
authors.lastname: Guo
authors.forename: Qi
authors.initials: Q
authors.lastname: Wu
authors.forename: Hui Ming
authors.initials: HM
authors.lastname: Ge
authors.forename: Yong Chun
authors.initials: YC
authors.lastname: Song
authors.forename: Seik Weng
authors.initials: SW
authors.lastname: Ng
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xu
authors.forename: Ren Xiang
authors.initials: RX
authors.lastname: Tan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001688:Biological Products / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003208:Concanavalin A / Q000037:antagonists & inhibitors / Q000494:pharmacology; D047630:Depsipeptides / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D005260:Female; D007113:Immunity, Innate; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D003904:Mitosporic Fungi / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
chemical_list: D001688:Biological Products; D047630:Depsipeptides; D007166:Immunosuppressive Agents; C000590734:trichomide A; D003208:Concanavalin A
keywords: configuration determination; cyclodepsipeptide; p-Akt; phytopathogen; selective immunosuppression